This proposal describes studies to clarify the biochemical mode of action of selenium as an essential trace element and a dietary agent modifying the toxicity of environmental toxicants. Characterization of the selenium moiety in ovine erythrocyte glutathione peroxidase will involve degradation of covalently-modified derivatives of the 75Se-labeled enzyme to low molecular weight compounds suitable for identification. Reactivation of the apoenzyme following release of the selenium moiety with cyanide under mild conditions will be studied. The pathway for biosynthesis of the selenium moiety in glutathione peroxidase will also be studied. Isolation and characterization of unidentified protein-bound forms of selenium in rat tissues such as brain and testes will be done to seek new selenoproteins and new functions for selenium. The form of selenium in foods, particularly marine food fish, will be studied and the form of selenium accumulated with mercury in liver of mammals. The mechanism by which selenium and vitamin E modify the neurotoxicity and metabolism of methylmercury will also be studied. The adequacy of selenium in special food products used in therapeutic nutrition will be investigated in nutritional studies with rats. Further investigations on a cadmium-binding protein found in testes will be performed.